title: Low immunogenicity predicted for emerging avian-origin H7N9: implication for influenza vaccine design.
abstract: A new avian-origin influenza virus emerged near Shanghai in February 2013, and by the beginning of May it had caused over 130 human infections and 36 deaths. Human-to-human transmission of avian-origin H7N9 influenza A has been limited to a few family clusters, but the high mortality rate (27%) associated with human infection has raised concern about the potential for this virus to become a significant human pathogen. European, American, and Asian vaccine companies have already initiated the process of cloning H7 antigens such as hemagglutinin (HA) into standardized vaccine production vehicles. Unfortunately, previous H7 HA-containing vaccines have been poorly immunogenic. We used well-established immunoinformatics tools to analyze the H7N9 protein sequences and compare their T cell epitope content to other circulating influenza A strains as a means of estimating the immunogenic potential of the new influenza antigen. We found that the HA proteins derived from closely related human-derived H7N9 strains contain fewer T cell epitopes than other recently circulating strains of influenza, and that conservation of T cell epitopes with other strains of influenza was very limited. Here, we provide a detailed accounting of the type and location of T cell epitopes contained in H7N9 and their conservation in other H7 and circulating (A/California/07/2009, A/Victoria/361/2011, and A/Texas/50/2012) influenza A strains. Based on this analysis, avian-origin H7N9 2013 appears to be a "stealth" virus, capable of evading human cellular and humoral immune response. Should H7N9 develop pandemic potential, this analysis predicts that novel strategies for improving vaccine immunogenicity for this unique low-immunogenicity strain of avian-origin influenza will be urgently needed.
authors.affiliation: Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA; EpiVax, Inc.; Providence, RI USA.
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.forename: Matthew
authors.initials: M
authors.lastname: Ardito
authors.forename: Frances
authors.initials: F
authors.lastname: Terry
authors.forename: Lauren
authors.initials: L
authors.lastname: Levitz
authors.forename: Ted
authors.initials: T
authors.lastname: Ross
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.forename: William
authors.initials: W
authors.lastname: Martin
mesh_terms: D000818:Animals; D001717:Birds; D017124:Conserved Sequence; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000276:immunology* / Q000302:isolation & purification*; D005585:Influenza in Birds / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D015047:Zoonoses / Q000276:immunology / Q000821:virology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: H7N9; Immunoinformatics; Influenza; T Cell Epitope; Vaccine; Vaccine Design; emerging infectious diseases